[unreadable] This proposal is to develop a power M-mode Doppler ultrasound device for monitoring blood flow in the basal arteries of the brain for embolic events, and characterizing these emboli as gas bubbles or particulates. This device is of significant value in several venues where medical procedures result in emboli going to the brain. Substantial clinical significance of embolus characterization is found in surgeries utilizing cardiopulmonary bypass, for which numerous outcomes studies have documented short and long term cognitive decline. Approximately one third of strokes associated with CPB are intra operative[l], a majority of which are embolic. The effects of embolization are currently not appreciated until the patient comes out of anesthesia and manifests neurologic deficits in the intensive care unit, which is too late to take preventive or therapeutic action. Ultrasound differentiation of embolus composition during surgery is therefore of great value for appropriately responding to the type of emboliziation with therapy or modification in surgical approach or technique. This proposal is based on successful in vitro (flow phantom) and in vivo (characterization of emboli from prosthetic heart valves in a human subject) feasibility experiments for Doppler ultrasound discrimination of gas bubbles and particulates. The critical elements for this technology are: (1) a high dynamic range Doppler ultrasound platform capable of processing Doppler shifts from fundamental and second harmonic reflections from moving scatterers and (2) a transducer with similar sensitivity patterns at both fundamental and second harmonic frequencies. The proposed work is to further develop these critical elements by refinement of probe design, enhancement of signal processing of the fundamental and second harmonic echoes from emboli, and presentation of the characterization results to the operator in an easily appreciated image format. The system developed in this proposal will be tested in a series of experiments on a flow loop, an animal model of the human middle cerebral artery, and on human subjects undergoing Tran cranial Doppler evaluation for presence and severity of patent foramen ovale. These tests will include observation of single emboli and embolus showers, with variable embolus size and composition. This work is anticipated to result in improved neurological outcomes in the targeted heart surgery application, and a Phase III partner is ready and waiting to take the technology to market. [unreadable] [unreadable]